Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We retrospectively investigated the outcomes of HLA-matched unrelated BMT (MU-BMT, n = 13) and HLA-identical sibling donor BMT (MS-BMT, n = 17) for childhood AML in CR1 between June 2002 and August 2005. Engraftment of neutrophil and platelet did not differ between the two transplant groups. The cumulative incidence of grade II-IV acute GVHD and any chronic GVHD at three yr was not different between MS-BMT and MU-BMT. Of the 30 patients, four patients experienced relapses (three with MS-BMT, one with MU-BMT) and four patients died of transplant-related complications (two with MS-BMT, two with MU-BMT). A total of 23 patients survived with a median follow-up of 43.2 months. The Kaplan-Meier estimates for EFS rates at three yr were 71% and 77% for MS-BMT and MU-BMT, respectively, and the OS rates were 76% and 77% for MS-BMT and MU-BMT, respectively. The outcome of HLA-matched unrelated BMT is comparable to that of HLA-identical sibling BMT for childhood AML in CR1. HLA-matched unrelated BMT may be recommended for patients who have AML in CR1 without an HLA-matched sibling donor.
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PMID:Comparable outcomes of HLA-matched unrelated and HLA-identical sibling donor bone marrow transplantation for childhood acute myeloid leukemia in first remission. 1862 12

Administration of alkylating agents (Alk), topoisomerase II inhibitors (Topo II) and radiotherapy (RT) can result in therapy-related myelodysplastic syndrome or acute myelogenous leukaemia (t-MDS/t-AML), the optimal treatment for which is allo-SCT. A retrospective review was performed of 24 patients who underwent related- or unrelated-donor SCT for t-MDS/t-AML at our institution. Eight patients remain alive and in continuous remission (median follow-up 54 months (range, 12-161)) with estimated 5-year EFS being 30% (95% confidence intervals 16-58%). Corresponding actuarial risks of relapse and non-relapse mortality (NRM) are 39% (19-60%) and 30% (13-50%), respectively. EFS was 40% in Alk/RT-related t-MDS/t-AML and 11% in Topo II-related t-MDS/t-AML (P=0.05), with an increased risk of relapse in the latter (56 vs 29%, respectively (P=0.05)). In multivariate analysis, development of acute GVHD (P=0.009) and Topo II-related t-MDS/t-AML (P=0.018) were associated with inferior EFS. Patients with acute GVHD had an increased risk of NRM (P=0.03) whereas risk of relapse was higher for patients of advanced age (P=0.046) and for patients who underwent bone marrow (vs blood) SCT (P=0.032). Allo-SCT can result in long-term survival for individuals with t-MDS/t-AML although outcome in Topo II-related t-MDS/t-AML patients remains suboptimal.
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PMID:Predictors of outcome following myeloablative allo-SCT for therapy-related myelodysplastic syndrome and AML. 1867 72

EFS for children with ALL continues to increase and is predicted to reach 90% with current therapy. Better understanding of leukemia cell biology and pharmacogenetics has led to the design of more effective treatment and also refined the prognostic features associated with a poor outcome. ALL characterized by the translocation t(9;22) or t(4;11), or by a hypodiploid karyotype or by an incomplete response to induction therapy is likely to relapse. SCT for ALL is largely used to treat patients failing primary chemotherapy but is selectively included as part of initial therapy for children at high risk for relapse. If SCT is going to become the primary therapy for children with ALL in first remission, the regimen-related mortality must approach 0%, and the risk for severe acute and chronic GVHD should be less than 5%. Salvage therapy after ALL relapse remains the major indication for SCT. The time required to find a suitable match has led to the use of cord blood and haploidentical related donors as stem cell sources. For children who relapse, SCT is likely to remain the principal option to promote survival. Efforts to reduce both the risk of relapse and the transplant regimen toxicity, both immediate and delayed, must continue.
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PMID:Transplantation for children with acute lymphoblastic leukemia. 1872 93

Allogeneic HSCT is a curative treatment for high-risk leukemia. In Europe, approximately 15% of children have an HLA-matched sibling, but in 65-70% HLA allele-matched (9-10/10) unrelated donors (UD) can be identified. Transplantation using an HLA partially mismatched donor, unrelated cord blood or haploidentical family donor with graft manipulation is then considered with preference on the basis of local experience and/or availability. Here we evaluate the outcomes of 87 consecutive patients with leukemia transplanted with unmanipulated graft from matched or partially mismatched UD or cord blood (CB) at our institution between January 2001 and December 2007. Within the median follow-up of 30 months, the acute GVHD grade II was diagnosed in 70.9% patients; grades III-IV only in 4.6%. The overall incidence of chronic GVHD was 43.3% (extensive in 34.9%). The probability of 3-year EFS was 59.5% and that of 3-year overall survival was 66.9%. TRM at day +100 was 4.5%, and overall it was 13.8%. Fourteen patients (16.1%) died as a consequence of post-transplant leukemia relapse. We conclude that the prognosis of patients transplanted for leukemia using unmanipulated grafts from HLA-matched or partially mismatched UD or CB is comparable and satisfactory. TRM and relapse rate are lower than in the earlier period.
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PMID:Allo-SCT in children with high-risk leukemia using unmanipulated grafts from alternative donors. 1897 35

We reviewed 26 consecutive patients with AML who were transplanted in second CR2 between 1994 and 2005. The most common conditioning regimen was CY and TBI. Median age at transplant was 8.9 yr (range 2.2-18.2). Nine patients received related donor, 16 patients received unrelated donors, and one patient received unrelated cord stem cells. Acute grade III-IV and chronic extensive GVHD occurred in eight (30%) and nine (35%) patients, respectively. Six patients (23%) relapsed, four of them died. Six patients (23%) died from TRM. Estimate of three-yr EFS was 0.53 (95% CI; 0.34-0.72). Including the two relapsed patients who were salvaged by DLI and second transplantation, three-yr OS was 0.61 (95% CI; 0.41-0.78) with a median follow-up of three and a half yr (range 1.5-11.2 yr). When entering remission, children with relapsed AML have a reasonable survival with HSCT, but relapse and TRM remain a concern.
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PMID:Outcome of allogeneic hematopoietic stem cell transplantation for children with acute myelogenous leukemia in second complete remission: single center experience. 1903 10

We studied the outcome of individuals with aplastic anaemia (AA) who received reduced-intensity conditioning followed by the infusion of stem cell grafts that had been T-cell depleted ex vivo with alemtuzumab. Consecutive patients with AA who had an HLA-identical sibling received conditioning with fludarabine 30 mg/m(2) daily for 5 days followed by CY 60 mg/kg on 2 consecutive days. Cytokine-mobilized blood grafts were incubated ex vivo with alemtuzumab 'in the bag' and infused without washing. CYA was prescribed until day +90. Engraftment rate, GVHD, EFS and overall survival were studied. Fifteen patients received PBPC grafts. It was the second graft in one of the patients. Ten patients were male and their median age was 23.5 years. The toxicity of the conditioning was minimal. One patient received 1 x 10(7)/kg donor lymphocytes for rising chimerism. At a median of 1107 (294-1778) days, all of them survived with normal blood parameters. None of them developed acute or chronic GVHD. In patients with AA the combination of purine analogue and alkylator leads to rapid engraftment despite T-cell depletion of grafts. This strategy of reduced-intensity conditioning has low toxicity, does not compromise engraftment and seems effective for prevention of GVHD.
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PMID:Reduced-intensity conditioning for severe aplasia using fludarabine and CY followed by infusion of ex vivo T-cell-depleted grafts leads to excellent engraftment and absence of GVHD. 1907 15

As unrelated allogeneic umbilical cord blood transplantation (UCBT) has been developed for 20 years already since 1988, more than ten thousands cases have cumulatively undergone UCBT over the world. A huge number of clinical data confirmed that UCBT had unique characters with low rate of severe GVHD. The efficacy and data on TRM, relapse and EFS of allogeneic UCBT with HLA 0-1 mismatched are similar to those in HLA matched BMT. UCBT has become the optimal choice for source of hematopoietic stem cells for allogeneic stem cell transplant especially when HLA-matched or haploidentical donors are not available in time. In most developed countries, unrelated allogeneic UCBT developed successively, and in recent years HLA mismatched UCBT with double units performed in adults increased even more rapidly than in children. Another recent trend of UCBT has been extending to treat some non-malignant but refractory diseases in pediatrics, such as severe combined immunodeficiency, thalassemia major, bone marrow failure syndrome and metabolic disorders. The clinical successful practice of double units for cord blood transplantation inspires to ponder over questions remaining mystery. What is the conflict like between two mismatched donor cells in vivo, which does not spoil the whole transplantation but enable the patient to be engrafted successfully without any increment of the dosage by the sum of two doses together? How can they both be taken at the same time firstly by the recipient, but why does only one predominate later? What are the factors enable the donor cells of the winner to sustain? With the references of the international experiences, how to solve the clinical encountered problems, perspective of unrelated allogeneic UCBT and proper strategies to be enacted are reviewed.
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PMID:[Unrelated allogeneic umbilical cord blood transplantation: present status, problems and countermeasures]. 1923 36

The transplant policy for unrelated donor (UD) BMT at Leiden Paediatrics' SCT-Centre consisted of the use of (1) fully HLA-matched donors or, if not available, HLA-class I matched and/or cytotoxic T-lymphocyte precursor (CTLp)-negative donors and (2) protective isolation of the recipient and antimicrobial suppression of his/her gut microflora to prevent infections and acute GVHD. Engraftment, GVHD, relapse in the case of malignancy and survival were studied retrospectively in 126 evaluable children, transplanted between 1988 and 2005. In addition to the effect of HLA-matching, that of other transplant-relevant variables on the outcome was also studied. Actuarial OS was 65% and the EFS was 59%, 13% graft failures occurred and 7.5% > or =grade II acute GVHD. HLA-class II mismatches combined with HLA-class I matches resulted in a superior OS of 92%, as did a negative vs positive CTLp test, that is, 65 vs 33%. Analysis of other variables showed a poorer OS in patients > or =10 yrs vs <10 yrs, that is, 54 vs 73%, and in male recipients of a female donor graft, that is, 53 vs 69% for other combinations. UD-BMT can be optimized by permitting HLA-class I-matched and/or CTLp-negative donors, and probably by choosing male donors for male recipients.
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PMID:Unrelated donor marrow transplantation in children: transplant policy and outcome in Leiden Paediatrics SCT-Centre. 1944 80

We analyzed the late outcomes of 429 long-term survivors post allogeneic hematopoietic SCT (allo-HSCT) who received transplant in our center between 1981 and 2002, and were free of their primary disease for > or =2 years after allo-HSCT. Late recurrent primary malignancy was found in 58 (13.5%) patients and was the primary cause of late death. A total of 37 (8.6%) patients died of non-relapse causes at a median of 5.5 years (range, 2-15.6 years) post allo-HSCT. The major non-relapse causes of death were chronic GVHD (cGVHD), secondary malignancy and infection. The probabilities of OS and EFS were 85% (95% cumulative incidence (CI) (81-89%)) and 79% (95% CI (74-83%)) at 10 years, respectively. Long-term allo-HSCT survivors were evaluated for late complications (median follow-up, 8.6 years (range, 2.3-22.8 years)). cGVHD was diagnosed in 196 (53.1%) survivors. The endocrine and metabolic complications were hypogonadism in 134 (36.3%) patients, osteopenia/osteoporosis in 90 (24.4%), dyslipidemia in 33 (8.9%), hypothyroidism in 28 (7.6%) and diabetes in 28 (7.6%). Hypertension was diagnosed in 79 (21.4%), renal impairment in 70 (19.0%), depression in 40 (10.8%) and sexual dysfunction in 33 (8.9%) survivors. We conclude that in patients who receive allo-HSCT as treatment for hematological malignancy and who are free of their original disease 2 years post transplant, mortality is low and the probability of durable remission is high. Lifelong surveillance is recommended.
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PMID:Long-term outcome after allo-SCT: close follow-up on a large cohort treated with myeloablative regimens. 1959 25

The relationship between tacrolimus concentration and acute GVHD is not well known, with few published data available for lower target levels. We hypothesized that lower levels of tacrolimus would correlate with higher incidence of acute GVHD and poorer prognosis. Receiver operator characteristic curves (ROC) were used to quantify tacrolimus blood levels as predictors of grade II-IV acute GVHD. A total of 97 pediatric patients with hematological malignancies met the study criteria. On the ROC, a cutoff of 7 ng/ml provided the best balance between sensitivity and specificity (62.8 vs 68.2%, respectively). Cumulative incidence of acute GVHD was 65.9% (range 58.5-73.3%) in patients with mean tacrolimus concentration of < or =7 ng/ml and 34.8% (range 27.8-41.8%) in patients with mean tacrolimus concentration of >7 ng/ml (P=0.002). Incidence of non-relapse mortality (NRM) was higher in patients with tacrolimus of < or =7 ng/ml (42.9%; range 35.6-50.2%) than in patients with tacrolimus of >7 ng/ml (28.3%; range 17.4-39.2%; P=0.008). This translated into better EFS in patients with tacrolimus of >7 ng/ml (48.9%; range 39.8-58.0%) than in patients with tacrolimus of < or =7 ng/ml (31.8%; range 25.0-38.6%; P=0.031). Multivariate analysis showed that tacrolimus concentration was significantly associated with clinical outcomes. Mean whole-blood level of tacrolimus as continuous infusion should be maintained at > or =7 ng/ml for pediatric patients.
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PMID:Relationship between tacrolimus blood concentrations and clinical outcome during the first 4 weeks after SCT in children. 1991 26


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